The asymmetric aldol addition mediated by a chiral auxiliary is one of the most commonly used reactions to form a carbon-carbon bond and two chiral carbons adjacent to a carbonyl group stereoselectively (see, Arya and Qin, Tetrahedron 2000, 56, 917-947; Evans et al., Top. Stereochem. 1982, 13, 1-115; Ager et al., Chem. Rev. 1996, 96, 835-875). Several methodologies and chiral auxiliaries have been developed for this endeavor; particularly dibutylboron enolates of N-acyloxazolidinones have been valuable to prepare the Evans syn-propionate aldol products (see, Evans et al., J. Am. Chem. Soc. 1981, 103, 2127-2129; Oppolzer et al., J. Am. Chem. Soc. 1990, 112, 2767-2772; and Sibi et al., Tetrahedron Lett. 1995, 36, 8965-8968). Utilizing the same chiral auxiliary, titanium(IV) enolates of N-acyloxazolidinones were shown to provide the non-Evans syn-propionate aldol products (see, Walker and Heathcock, J. Org. Chem. 1991, 56, 5747-5750; Bonner and Thornton, J. Am. Chem. Soc. 1991, 113, 1299-1308; and Yan et al., J. Am. Chem. Soc. 1993, 115, 2613-2621). Recent reports suggest that by using chlorotitanium(IV) enolates of N-propionate thiazolidinethiones we can access the Evans syn-aldol product when adding one equivalent of sparteine, and the non-Evans syn-aldol product when adding two equivalents of the same base (see, Crimmins et al., J. Am. Chem. Soc. 1997, 119, 7883-7884; and Crimmins et al., J. Org. Chem. 2001, 66, 894-902). This change in facial selectivity is the result of switching mechanistic pathways between chelated and non-chelated transition states. Evans reported the anti-aldol reaction promoted by catalytic amounts of magnesium halide in the presence of triethylamine and chlorotrimethylsilane. (see, Evans et al., J. Am. Chem. Soc. 2002, 124, 392-393; and Evans et al., Org. Lett. 2002, 4, 1127-1130). These conditions deliver the Evans anti-aldol product when using an oxazolidinone, and the opposite aldol product when using a thiazolidinethione.
Chiral auxiliary driven acetate-type aldol reactions have proven more difficult than the corresponding propionate reactions. N-Acetate oxazolidinones and other chiral auxiliaries did not provide the diastereoselectivities achieved with the corresponding N-propionates (see, Nerz-Stormes and Thornton, Tetrahedron Lett. 1986, 27, 897-900; Masamune et al., Angew. Chem., Int. Ed. 1985, 24, 1-XX; and Braun, Angew. Chem., Int. Ed. Eng. 1987, 26, 24-37). Several methods and strategies have been realized to solve this problem. Among them, Nagao's acetate aldol reaction with tin enolate of N-acetyl thiazolidinethione delivered high diastereoselectivities (see, Nagao et al., J. Chem. Soc., Chem. Commun. 1985, 1418; Nagao et al., J. Org. Chem. 1986, 51, 2391-2393; Velasquez and Olivo, Curr. Org. Chem. 2002, 6, 303-340; and Ortiz and Sansinenea, J. Sulfur Chem. 2007, 28, 109-147). However, the high price and irreproducibility of tin triflate prompted others to investigate other Lewis acids for this aldol reaction. The more economic titanium(IV) enolate was found to be highly efficient (see, Yan et al., J. Org. Chem. 1995, 60, 3301-3306; Gonzalez et al., Tetrahedron Lett. 1996, 37, 8949-8952; Crimmins et al., Org. Lett. 1999, 1, 2029-2032; Romero-Ortega et al., Tetrahedron Lett. 2002, 43, 6439-6441; and Hodge and Olivo, Tetrahedron 2004, 60, 9397-9403). More sterically encumbered thiazolidinethiones and oxazolidinethiones have also been prepared to deliver higher diastereoselectivities, albeit at a higher price for starting materials and or longer reaction sequences (see, Guz and Phillips, Org. Lett. 2002, 4, 2253-2256; Zhang et al., Org. Lett. 2004, 6, 23-25; Zhang and Sammakia, Org. Lett. 2004, 6, 3139-3141; and Crimmins and Shamszad, Org. Lett. 2007, 9, 149-152).
Therefore, there exists a need in the art to address the preceding shortcomings of the art, in particular with respect to the facile and lower-cost preparation of chiral auxiliaries which show diastereoselectivity when utilized as N-acetate enols.